Treating EGFR-Mutated Oncogene-Addicted Advanced Non-Small-Cell Lung Cancer in the Era of Economic Crisis in Greece: Challenges and Opportunities.

PURPOSE: Because of the profound financial crisis that commenced in Greece in 2010, severe cuts in health care spending and other restriction measures led to significant delays in the reimbursement of novel antineoplastic agents. In 2011, the Hellenic Society of Medical Oncology initiated a program of early access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the treatment of patients with advanced, EGFR-mutant non-small-cell lung cancer (NSCLC). We evaluated treatment patterns and clinical outcomes in patients with EGFR-mutant or wild-type disease treated at a large center in Greece throughout the period of financial crisis. PATIENTS AND METHODS: From 2011 through 2015, 252 patients with newly diagnosed advanced NSCLC were treated at the Department of Medical Oncology of the Papageorgiou Hospital, a tertiary cancer center in northern Greece. We retrospectively reviewed patient medical records to obtain clinicopathologic characteristics, EGFR mutation status, and follow-up data. The primary end point was time to treatment failure. RESULTS: Of the 198 evaluable patients, 25 (12%) had EGFR mutations. All patients with EGFR mutations except one received treatment with an EGFR tyrosine kinase inhibitor. Median times to treatment failure for patients with EGFR-mutant and wild-type disease were 15.8 and 7.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.35 to 0.95; P = .031). There was no difference in overall survival between the two groups ( P = .293). No deviation from treatment guidelines or discontinuation of treatment regimens occurred because of logistic reasons or drug shortages. CONCLUSION: Despite restrictions in the reimbursement policy and accompanying controls in the use of high-cost medicines, the national program enabled treatment of patients with EGFR-mutant NSCLC according to established guidelines. Therefore, the clinical outcomes of such patients treated in Greece during the economic crisis were in accordance with international standards.

Targeted KRAS mutation assessment on patient tumor histologic material in real time diagnostics.

BACKGROUND: Testing for tumor specific mutations on routine formalin-fixed paraffin-embedded (FFPE) tissues may predict response to treatment in Medical Oncology and has already entered diagnostics, with KRAS mutation assessment as a paradigm. The highly sensitive real time PCR (Q-PCR) methods developed for this purpose are usually standardized under optimal template conditions. In routine diagnostics, however, suboptimal templates pose the challenge. Herein, we addressed the applicability of sequencing and two Q-PCR methods on prospectively assessed diagnostic cases for KRAS mutations. METHODOLOGY/PRINCIPAL FINDINGS: Tumor FFPE-DNA from 135 diagnostic and 75 low-quality control samples was obtained upon macrodissection, tested for fragmentation and assessed for KRAS mutations with dideoxy-sequencing and with two Q-PCR methods (Taqman-minor-groove-binder [TMGB] probes and DxS-KRAS-IVD). Samples with relatively well preserved DNA could be accurately analyzed with sequencing, while Q-PCR methods yielded informative results even in cases with very fragmented DNA (p<0.0001) with 100% sensitivity and specificity vs each other. However, Q-PCR efficiency (Ct values) also depended on DNA-fragmentation (p<0.0001). Q-PCR methods were sensitive to detect99%) could accurately be analyzed at a sensitivity level of 10% (external validation of TMGB results). DNA quality and tumor cell content were the main reasons for discrepant sequencing/Q-PCR results (1.5%). CONCLUSIONS/SIGNIFICANCE: Diagnostic targeted mutation assessment on FFPE-DNA is very efficient with Q-PCR methods in comparison to dideoxy-sequencing. However, DNA fragmentation/amplification capacity and tumor DNA content must be considered for the interpretation of Q-PCR results in order to provide accurate information for clinical decision making.